Density functional theory (DFT) calculations and an experimental vibrational characterization of papaverine hydrochloride were performed. The computed structural parameters agree very well with the experimental values of the related crystal structure. The pH dependent Raman and SERS spectra of papaverine hydrochloride were recorded and discussed with the assistance of our theoretical results (harmonical vibrational wavenumbers, Raman scattering activities, total electron density and Natural Population Analysis of the molecule) and the SERS surface selection rules. Two different adsorption geometries were found for the corresponding evidenced species of papaverine, protonated and neutral, respectively.